The structure of feared social situations among race-ethnic minorities and Whites with social anxiety disorder in the United States

We investigated feared social situations in individuals with social anxiety disorder from different racial and ethnic groups in the United States. The sample included 247 African Americans, 158 Latinos, and 533 non-Latino Whites diagnosed with social anxiety disorder within the past 12 months from the integrated Collaborative Psychiatric Epidemiology Studies data set. After randomly splitting the full sample, we conducted an exploratory factor analysis with half of the sample to determine the structure of feared social situations in a more diverse sample than has been used in previous studies. We found evidence for a model consisting of three feared social domains: performance/public speaking, social interaction, and observational. We then conducted a confirmatory factor analysis on the remaining half of the sample to examine whether this factor structure varied significantly between the race-ethnic groups. Analyses revealed an adequate fit of this model across all three race-ethnic groups, suggesting invariance of the factor structure between the study groups. Broader cultural contexts within which these findings are relevant are discussed, along with important implications for comprehensive, culturally sensitive assessment of social anxiety.R01 MH078308 - NIMH NIH HHS; R01 MH081116 - NIMH NIH HHS; MH-081116 - NIMH NIH HHS; K23 MH096029 - NIMH NIH HHS; MH-078308 - NIMH NIH HH

Distinguishing features of cetuximab and panitumumab in colorectal cancer and other solid tumors

Cetuximab and panitumumab are two distinct monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR), and both are widely used in combination with chemotherapy or as monotherapy to treat patients with RAS wild-type metastatic colorectal cancer. Although often considered interchangeable, the two antibodies have different molecular structures and can behave differently in clinically relevant ways. More specifically, as an immunoglobulin (Ig) G1 isotype mAb, cetuximab can elicit immune functions such as antibody-dependent cell-mediated cytotoxicity involving natural killer cells, T-cell recruitment to the tumor, and T-cell priming via dendritic cell maturation. Panitumumab, an IgG2 isotype mAb, does not possess these immune functions. Furthermore, the two antibodies have different binding sites on the EGFR, as evidenced by mutations on the extracellular domain that can confer resistance to one of the two therapeutics or to both. We consider a comparison of the properties of these two antibodies to represent a gap in the literature. We therefore compiled a detailed, evidence-based educational review of the known molecular, clinical, and functional differences between the two antibodies and concluded that they are distinct therapeutic agents that should be considered individually during treatment planning. Available data for one agent can only partly be extrapolated to the other. Looking to the future, the known immune activity of cetuximab may provide a rationale for this antibody as a combination partner with investigational chemotherapy plus immunotherapy regimens for colorectal cance

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

Applying the Cry of Pain model as a predictor of deliberate self-harm in an early-stage adult male prison population

Purpose: Deliberate self-harming behaviour is more prevalent within the prison environment than in community samples, with those in the first weeks of imprisonment at greatest risk. Research in this area has been largely atheoretical and a unifying model may improve the predictability of assessment and the development of intervention approaches. This study applied William and Pollock’s (2001) Cry of Pain model as the theoretical process of deliberate self-harm in the early stages of imprisonment. Method: A prospective study of new arrivals at an adult male prison. Participants (n =181) completed questionnaires and it was hypothesised that the factors derived from the model (perceived stress, defeat, entrapment and absence of rescue factors) would be predictive of future deliberate self-harm. Prisoners with active psychosis and non-English speakers were excluded. All participants were followed up for four months for instances of self-harm. Eighteen participants engaged in self-harm during this period. Results: The Cry of Pain Model was supported in the analysis. Hierarchical binary logistic regression confirmed that all features of the model were supported as predictive of future self-harm in prison, even after controlling for previous self-harm, depression and hopelessness. Conclusion: The Cry of Pain model is supported as a predictive model for deliberate self-harm in prison. Suggestions are offered as to the impact on assessment and intervention directions in prison

Transport and binding of tumor necrosis factor-α in articular cartilage depend on its quaternary structure

The effect of tumor necrosis factor-α (TNFα) on cartilage matrix degradation is mediated by its transport and binding within the extracellular matrix (ECM) of the tissue, which mediates availability to cell receptors. Since the bioactive form of TNFα is a homotrimer of monomeric subunits, conversion between trimeric and monomeric forms during intratissue transport may affect binding to ECM and, thereby, bioactivity within cartilage. We studied the transport and binding of TNFα in cartilage, considering the quaternary structure of this cytokine. Competitive binding assays showed significant binding of TNFα in cartilage tissue, leading to an enhanced uptake. However, studies in which TNFα was cross-linked to remain in the trimeric form revealed that the binding of trimeric TNFα was negligible. Thus, binding of TNFα to ECM was associated with the monomeric form. Binding of TNFα was not disrupted by pre-treating cartilage tissue with trypsin, which removes proteoglycans and glycoproteins but leaves the collagen network intact. Therefore, proteoglycan loss during osteoarthritis should only alter the passive diffusion of TNFα but not its binding interaction with the remaining matrix. Our results suggest that matrix binding and trimer–monomer conversion of TNFα both play crucial roles in regulating the accessibility of bioactive TNFα within cartilage.National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR45779)National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR60331

Biased distance estimation in social anxiety disorder: A new avenue for understanding avoidance behavior

Objectives: People regulate their interpersonal space appropriately to obtain a comfortable distance for interacting with others. Socially anxious individuals are especially prone to discomfort from and fear of physical closeness, leading them to prefer a greater interpersonal distance from others. Previous studies also indicate that fear can enhance the threat-related elements of a threatening stimulus. For example, spider phobia is associated with estimating spiders as bigger and faster than they actually are. Nonetheless, it is still unclear whether the preference of those with social anxiety disorder (SAD) to maintain greater distance from others is associated with biased estimations of interpersonal distance.Materials and methods: A total of 87 participants (44 clinically diagnosed with SAD and 43 control) performed validated computerized and ecological tasks in a real-life setting while social space estimations and preferences were measured.Results: Participants with SAD felt comfortable when maintaining a greater distance from unfamiliar others compared to the control group and estimated unfamiliar others to be closer to them than they actually were. Moreover, the estimation bias predicted their preferred distance from strangers, indicating a strong association between estimation bias severity and actual approach-avoidance behavior.Conclusion: Our findings indicate that distance estimation bias underlies avoidance behavior in SAD, suggesting the involvement of a new cognitive mechanism in personal space regulation

Perception of interpersonal distance and social distancing before and during COVID-19 pandemic

Since COVID-19 is easily transmitted among people in close physical proximity, the focus of epidemiological policy during the COVID-19 crisis included major restrictions on interpersonal distance. However, the way in which distance restrictions affected spatial perception is unclear. In the current study, we examined interpersonal distance preferences and perceptions at three time points: pre-pandemic, early post-pandemic, and late post-pandemic. The results indicate that following the pandemic outbreak, people perceived others as farther away than they actually were, suggesting that the distance restrictions were associated with an enlargement of perceived interpersonal distance. Interestingly, however, people maintained the same distance from one another as before the outbreak, indicating no change in actual distance behavior due to the risk of infection. These findings suggest that COVID-19 was associated with a change in the way distance is perceived, while in practice, people maintain the same distance as before. In contrast, COVID-related anxiety predicted both a preference for maintaining a greater distance and a bias toward underestimating perceived distance from others. Thus, individuals who were highly fearful of COVID-19 perceived other people to be closer than they actually were and preferred to maintain a larger distance from them. The results suggest that subjective risk can lead to an increased perception of danger and a subsequent change in behavior. Taken together, even when behaviors should logically change, the decision-making process can be based on distorted perceptions. This insight may be used to predict public compliance

The Take Control Course : conceptual rationale for the development of a transdiagnostic group for common mental health problems

Background: Increasingly, research supports the utility of a transdiagnostic understanding of psychopathology. However, there is no consensus regarding the theoretical approach that best explains this. Transdiagnostic interventions can offer service delivery advantages; this is explored in the current review, focusing on group modalities and primary care settings. Objective: This review seeks to explore whether a Perceptual Control Theory (PCT) explanation of psychopathology across disorders is a valid one. Further, this review illustrates the process of developing a novel transdiagnostic intervention (Take Control Course; TCC) from a PCT theory of functioning. Method: Narrative review. Results and Conclusions: Considerable evidence supports key tenets of PCT. Further, PCT offers a novel perspective regarding the mechanisms by which a number of familiar techniques, such as exposure and awareness, are effective. However, additional research is required to directly test the relative contribution of some PCT mechanisms predicted to underlie psychopathology. Directions for future research are considered

Suppressive effect of TNF-α and IL-1 on alveolar fibroblast proliferation in sarcoidosis

The nature of soluble factors that regulate fibroblast proliferation have not been finally characterized. Our aim was to study the role of tumour necrosis factor α (TNF-α) and interleukin-1 (IL-1) in the suppressive activity of alveolar macrophages on autologous lung fibroblasts proliferation in sarcoidosis. We found that supernatants recovered from alveolar macrophages suppressed the proliferation of alveolar fibroblast in sarcoidosis by 35.5 ± 1.13% compared to 3 ± 16% in controls (p < 0.001 between the two groups). This suppression correlated with high content of TNF-α and IL-1 in sarcoidosis patients stage II-III (7.7 ± 2.9 ng/ml TNF-α and 157 ± 53 U/ml IL-1 compared to 3.4 ± 2.4 ng/ml TNF-α and 43 U/ml IL-1 in controls; p < 0.01 and p < 0.001, respectively). Both cytokines in sarcoidosis stage I were within the normal ranges. Exogenous TNF-α (1000-0.5 ng/ml) and IL-1 (500-0.24 ng/ml) had an additive suppressive activity on fibroblast proliferation which was partially reversed by indomethacin